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We thank Drs. Ansley and Xia for their interest in our recent article 1 and for reviewing their results regarding cardioprotective effects of propofol. 2,3 They proffered that volatile anesthetic-induced reactive oxygen species (ROS) formation (required for the triggering of anesthetic preconditioning [APC]) might be deleterious in patients with a preexisting high degree of oxidative stress and, furthermore, that APC is unlikely to be of benefit in high-risk patients whose antioxidant capacity is reduced.

Our isolated heart experiments do not support such a postulate. First, the amount of ROS generated in the heart during exposure to a volatile anesthetic is miniscule compared with that generated during ischemia–reperfusion. 4 This seems to make sense because we know that patients, even high-risk patients, can receive volatile anesthetic agents for many hours without evidence of myocardial injury, and these agents have a record of safety stretching back 50 yr. This would probably not be the case if ROS generation in response to volatile anesthetics were inherently deleterious. Second, APC, although triggered by a small pulse of ROS during exposure to the volatile anesthetic, is characterized by a great reduction in the amount of ROS subsequently released during ischemia–reperfusion. 4,5 Therefore, actual exposure of the heart to ROS is greatly reduced after APC, and patients with reduced antioxidant defenses might be precisely those who stand to benefit most from APC.

Ansley and Xia comment that inhibition of myocyte Ca2+influx may contribute to the cardioprotective effect of propofol. This may be true, but a similar effect has been described for volatile anesthetic agents. 6 Furthermore, we have recently reported attenuated ischemic and post-ischemic mitochondrial
Ca2+loading in hearts previously treated with sevoflurane. 7 Given the known deleterious effects of mitochondrial Ca2+overload and the key role played by the mitochondrion in post-ischemic cellular integrity and function, this effect is likely to underlie, at least in part, the cardioprotective effect of APC.

Regarding prospective clinical trials comparing volatile anesthetic agents and propofol, two interesting studies were recently published in Anesthesiology. 8,9 In the first of these, 8 45 high-risk coronary surgery patients were randomly assigned to a primary anesthetic of propofol, sevoflurane, or desflurane. After cardiopulmonary bypass, cardiac index was found to be significantly higher in the sevoflurane and desflurane groups compared with the propofol group, and postoperative troponin I concentrations were lower, indicating less severe myocardial injury. In the second study, 9 20 patients undergoing off-pump coronary artery bypass surgery were randomized to receive propofol or sevoflurane as their primary anesthetic. In the sevoflurane group, postoperative troponin I concentrations were found to be significantly lower compared with the propofol group. Although these trials do not provide conclusive evidence of a preconditioning effect of volatile anesthetics, they do provide an enticing basis for further study. Other “direct” protective effects of the volatile anesthetics or a possible deleterious effect of propofol could have been responsible for the observed outcome differences. Although propofol is thought to have antioxidant effects, it should also be noted that many animal studies do not support a role for propofol as a preconditioning agent.10–14

Much work remains to be done in elucidating mechanisms and characteristics of cardioprotective effects of both types of anesthetics. The direct antioxidant effects of propofol may prove to be most advantageous during the reperfusion phase, when ROS generation by the heart is great and unquestionably injurious. The preconditioning effect of volatile agents suggests that their protective effect is maximal when administered before ischemia. The future challenge for investigators is to find an optimal regimen for patients that fully exploits the cardioprotective effects identified in the laboratory.